Compounds useful in preparing camptothecin derivatives
AssigneePharmacia & Upjohn Company
InventorKevin E. Henegar
Life of this patent
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Abstract
Novel compounds are provided having the formula and salt thereof, where R1 is hydrogen, an alkyl, aralkyl, hydroxymethyl, carboxymethyl acyloxymethyl or trialkylsilyl group, or a group —CH2NR3R4 where N is a linking nitrogen atom and where (a) R3 and R4 are independently selected from hydrogen and alkyl, alkenyl, hydroxyalkyl and alkoxyalkyl groups; (b) R3 is hydrogen or an alkyl, alkenyl, hydroxyalkyl or alkoxyalkyl group, and R4 is —COR5 where R5 is hydrogen or an alkyl, alkenyl, hydroxyalkyl or alkoxyalkyl group; or (c) R3 and R4 taken together with the linking nitrogen atom form a saturated 3- to 7-member heterocyclic group. These compounds are useful intermediates in a process to prepare camptothecin derivatives including the anti-cancer drug irinotecan.
Claims10
A compound having the formula
- or a pharmaceutically acceptable salt thereof, where R1 is hydrogen, an alkyl, aralkyl, hydroxymethyl, carboxymethyl acyloxymethyl or trialkylsilyl group, or a group —CH2NR3R4 where N is a linking nitrogen atom and where (a) R3 and R4 are independently selected from hydrogen and alkyl, alkenyl, hydroxyalkyl and alkoxyalkyl groups;
- (b) R3 is hydrogen or an alkyl, alkenyl, hydroxyalkyl or alkoxyalkyl group, and R4 is —COR5 where R5 is hydrogen or an alkyl, alkenyl, hydroxyalkyl or alkoxyalkyl group;
- or (c) R3 and R4 taken together with the linking nitrogen atom form a saturated 3- to 7-member heterocyclic group.
A process for preparing irinotecan or a salt thereof, the process comprising a step of reacting 4-amino-3-propionylphenyl-1,4′-bipiperidine-1′-carboxylate or a salt thereof with the compound having the formula
A process for preparing 7-ethyl-10-hydroxycamptothecin or a salt thereof, the process comprising a first step of reacting 4-amino-3-propionylphenyl-1,4′-bipiperidine-1′-carboxylate or a salt thereof with the compound having the formula
- to form irinotecan or a salt thereof;
- and a second step of hydrolyzing the irinotecan or salt thereof in an acid medium to form 7-ethyl-10-hydroxycamptothecin or a salt thereof.
A process for preparing 4-amino-3-propionylphenyl-1,4′-bipiperidine-1′-carboxylate, the process comprising a step of reacting 1-(4-hydroxy-2-aminophenyl)-1-propanone with 4-piperidinopiperidinecarbamyl chloride.
Dependencies are inferred from the claim text.